The effects of betamethasone derivatives on endotoxin-induced uveitis in guinea pigs.
OBJECTIVE
We reported previously that the betamethasone derivative betamethasone dipropionate behaves as an anti-glucocorticoid in rat endotoxin-induced uveitis (EIU). In the present study, we produced EIU in guinea pigs and investigated the effects of betamethasone dipropionate on the EIU.


METHODS
Male Hartley guinea pigs were used.


METHODS
Glucocorticoids were instilled into the eye.


METHODS
To elicit EIU, lipopolysaccharide (LPS) was injected into the anterior chamber of the eye. Cell numbers in the aqueous humor after LPS injection were determined by flow cytometry. Prostaglandin E2 (PGE2) production after LPS injection into the anterior chamber was also examined.


RESULTS
Intracameral injection of LPS (1 microgram/eye) induced cell infiltration into the anterior chamber and PGE2 production. Betamethasone dipropionate inhibited cell infiltration and PGE2 production more strongly than betamethasone. These results suggest that betamethasone dipropionate is a potent glucocorticoid in guinea pigs.


CONCLUSIONS
Structure-activity relationships of glucocorticoids in the guinea pig EIL model may differ from those in the rat EIU model.
Tsuji
F
F
Discovery Research Division, Santen Pharmaceutical Co. Ltd., Osaka, Japan.
Sawa
K
K
Ikuse
T
T
Shirasawa
E
E
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001082:Aqueous Humor / Q000378:metabolism; D001623:Betamethasone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001624:Betamethasone Valerate / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004731:Endotoxins; D004926:Escherichia coli / Q000737:chemistry; D006168:Guinea Pigs; D007958:Leukocyte Count / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D014605:Uveitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D008070:Lipopolysaccharides; C044101:endotoxin, Escherichia coli; C011175:betamethasone-17,21-dipropionate; D001623:Betamethasone; D001624:Betamethasone Valerate; D015232:Dinoprostone